Valley fever, mimicker of malignancy.

Coccidioidomycosis rates in endemic areas such as California and Arizona have been increasing in recent years. Most common manifestations in symptomatic individuals involve the lungs. Disseminated disease occurs when the infection spreads beyond the lungs. Disseminated disease occurs in about 1% of all coccidiomycosis cases. Diagnosis in classically non-endemic regions can be difficult as coccidiomycosis can mimic a variety of other illnesses which can lead to delays in initiating appropriate therapy. We report a case of severe disseminated coccidiomycosis involving the soft tissue, bone, and intra-abdominal organs in a previously healthy individual that was initially thought to be a malignancy. With climate change possibly altering the traditional endemic regions and expanding Coccidioides to new territories, this case reinforces the importance of maintaining a broad differential as well as awareness of disease manifestations for healthcare providers who do not regularly treat Coccidioides.

Enhancing learning and retention with distinctive virtual reality environments and mental context reinstatement.

Memory is inherently context-dependent: internal and environmental cues become bound to learnt information, and the later absence of these cues can impair recall. Here, we developed an approach to leverage context-dependence to optimise learning of challenging, interference-prone material. While navigating through desktop virtual reality (VR) contexts, participants learnt 80 foreign words in two phonetically similar languages. Those participants who learnt each language in its own unique context showed reduced interference and improved one-week retention (92%), relative to those who learnt the languages in the same context (76%)-however, this advantage was only apparent if participants subjectively experienced VR-based contexts as "real" environments. A follow-up fMRI experiment confirmed that reinstatement of brain activity patterns associated with the original encoding context during word retrieval was associated with improved recall performance. These findings establish that context-dependence can be harnessed with VR to optimise learning and showcase the important role of mental context reinstatement.

The Posterior Atlantooccipital Membrane: The Anchor for the Myodural Bridge and Meningovertebral Structures.

INTRODUCTION: Sheet plastination has provided evidence that the posterior atlantooccipital membrane attaches to the dura's posterior sleeve at the cerebrospinal junction. These findings contradict the traditional anatomical description of this membrane extending from the atlas' posterior arch to the foramen magnum. METHODS: A total of 16 plastinated cadavers were studied to evaluate the in situ and gross configuration of the posterior atlantooccipital membrane. Fifteen cadavers underwent sheet plastination, and one head was hemisected and plastinated. In all specimens, stereomicroscopy was used to evaluate the posterior atlantooccipital membrane and related structures within the intervertebral and epidural spaces. RESULTS: In all 16 specimens, the posterior atlantooccipital membrane extending from the occiput, merged with the craniocervical dura mater, and formed a membrane-dura complex that ended at the level of the third cervical vertebra. The superior and inferior myodural bridge coalesced with their respective vertebrodural ligaments and fused with the posterior atlantooccipital membrane at their respective interspaces. CONCLUSION: The median aspect of the posterior atlantooccipital membrane does not directly communicate with the posterior arch of the atlas. Instead, the posterior atlantooccipital membrane converges with the craniocervical dura mater and terminates at the level of the third cervical vertebra. This membrane-dura complex serves as a common attachment site for the myodural and vertebrodural structures.

Medical Comorbidities Associated With Outcomes in Patients With Traumatic Epidural Hematomas.

Background Traumatic brain injury (TBI) is a frequently encountered neurosurgical pathology with significant morbidity and mortality. One such subtype is the epidural hematoma. Literature regarding the effects of comorbidities in TBI and epidural hematomas is limited. Methodology This was a single-center retrospective review of 50 consecutive patients admitted to a level two trauma center with epidural hematomas. Patients were identified using an internal trauma database. Patients were included if they were 18 years of age with a diagnosed epidural hematoma. Outcome variables of Glasgow coma scale (GCS), length of stay in the intensive care unit (ICU) and hospital, and requirement of a neurosurgical procedure were analyzed. Identification of the presence of diagnosed comorbidities was performed including common comorbidities such as obesity, diabetes, hypertension, hyperlipidemia, drug use, tobacco use, cancer, psychiatric disease, and renal disease. Correlations were evaluated using two-sided bivariate analysis (p < 0.05). Results A total of 50 patients were included for analysis. Significant correlations with a p-value less of than 0.05 were noted in initial GCS and cancer (r = -0.357, p = 0.011), requirements of an intracranial procedure with a history of gastrointestinal disease (r = 0.377, p = 0.007), and younger age (r = -0.306, p = 0.031). Increased ICU length of stay was related to a history of cancer (r = 0.494, p < 0.001), a history of respiratory disease (r = 0.427, p = 0.002), and a history of psychiatric disease (r = 0.297, p = 0.036). Increased hospital length of stay was related to psychiatric disorders (r = 0.285, p = 0.045). Discharge GCS was negatively associated with a history of hypertension (r = -0.374, p = 0.008), tobacco use (r = -0.417, p = 0.003), drug use (r = -0.294, p = 0.037), and history of cancer (r = -0.303, p = 0.032). Discussion and Conclusions In our 50 consecutive patient subset, selected comorbidities demonstrated significant relationships with outcome measures of GCS, need for a procedure, and lengths of stay in the hospital and ICU. Obtaining comorbidity information when available from families can better allow the clinician to optimize treatment and educate loved ones about the potential effects of these comorbidities on the overall health of the patient. Understanding these correlations may allow for a better understanding of the systemic effects of the pathophysiology of injury in epidural hematomas.

Retraction: Racial Disparity Amongst Stroke Patients During the Coronavirus Disease 2019 Pandemic.

[This retracts the article DOI: 10.7759/cureus.10369.].

Racial Disparity Amongst Stroke Patients During the Coronavirus Disease 2019 Pandemic.

Introduction The global coronavirus disease 2019 (COVID-19) pandemic has had deleterious effects on our healthcare system. Lockdown measures have decreased the number of patients presenting to the hospital for non-respiratory illnesses, such as strokes. Moreover, there appears to be a racial disparity among those afflicted with the virus. We sought to assess whether this disparity also existed for patients presenting with strokes. Methods The Get with the Guidelines National Stroke Database was reviewed to assess patients presenting with a final diagnosis of ischemic stroke, transient ischemic attack (TIA), subarachnoid hemorrhage (SAH), or spontaneous/nontraumatic intraparenchymal hemorrhage (IPH). The period of February - May 2020 was chosen given the surge of patients affected with the virus and national shutdowns. Data from this same time during 2019 was used as the control population. Our hospital numbers and four additional regions were assessed (California hospitals, Pacific State hospitals, Western Region hospitals, and all hospitals in the United States). Patients were categorized by race (White, Black/African American, Asian, Native American, Hispanic) in each cohort. The primary endpoint of this study is to compare whether there was a significant difference in the proportion of patients in each reported racial category presenting with stroke during the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results A downward trend in total number of patients was noted in all five regional cohorts assessed. A statistically significant increase in the number of Black and Hispanic patients presenting with strokes was noted in California, Pacific hospitals, Western hospitals, and all hospitals in the United States during various months studied comparing 2020 to 2019. A statistically significant increase in the Hispanic population was noted in February and March in all California hospitals (p=0.005 and 0.02, respectively) and Pacific Coast hospitals (p=0.005 and 0.039, respectively). The Western region and all national hospitals noted a significant increase in strokes in the Hispanic population in April (p=0.039 and 0.023, respectively). A statistically significant increase of strokes in the Black population was noted in April in Pacific hospitals, Western region hospitals, and all national hospitals (p=0.039, 0.03, and 0.03, respectively). Conclusion The COVID-19 pandemic has adversely affected certain racial groups more than others. A similar increase is noted in patients presenting with strokes in these specific racial populations. Moreover, lack of testing for the SARS-CoV-2 virus may be missing a possible link between racial disparity for patients infected with the virus and patients presenting with stroke. The authors advocate for widespread testing for all patients to further assess this correlation.

Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes.

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE). Astrocyte-specific RNAs from various neuroanatomic regions were attained using RiboTag technology. Sequencing and bioinformatics analyses showed that EAE-induced gene expression changes differed between neuroanatomic regions when comparing astrocytes from spinal cord, cerebellum, cerebral cortex, and hippocampus. The top gene pathways that were changed in astrocytes from spinal cord during chronic EAE involved decreases in expression of cholesterol synthesis genes while immune pathway gene expression in astrocytes was increased. Optic nerve from EAE and optic chiasm from MS also showed decreased cholesterol synthesis gene expression. The potential role of cholesterol synthesized by astrocytes during EAE and MS is discussed. Together, this provides proof-of-concept that a cell-specific and region-specific gene expression approach can provide potential treatment targets in distinct neuroanatomic regions during multifocal neurological diseases.

Inhibitory activities of the heterotrimers formed from two α-type phospholipase A2 inhibitory proteins with different enzyme affinities and importance of the intersubunit electrostatic interaction in trimer formation.

α-type phospholipase A2 inhibitory protein (PLIα) isolated from the serum of the venomous snake Glyoidius brevicaudus, GbPLIα, is a homotrimer of subunits having a C-type lectin-like domain. The serum protein from nonvenomous snake Elaphe quadrivirgata, EqPLIα-LP, is homologous to GbPLIα, but it does not show any inhibitory activity against PLA2s. When a mixture of denaturant-treated monomeric forms of GbPLIα and EqPLIα-LP was used to reconstitute their trimers, no significant amounts of heterotrimers composed of GbPLIα and EqPLIα-LP subunits could be formed. On the other hand, when a mixture of denaturant-treated monomeric forms of GbPLIα and the recombinant chimeric EqPLIα-LP, Eq13Gb37Eq, in which the residues 13-36 were replaced by those of GbPLIα, was used to reconstitute their trimers, significant amounts of their heterotrimers were observed. Furthermore, when a mixture of denaturant-treated monomeric forms of EqPLIα-LP and the recombinant chimeric GbPLIα, Gb13Eq37Gb, in which the residues 13-36 were replaced by those of EqPLIα-LP, was used, significant amounts of their heterotrimers were observed. By comparison of the respective inhibitory activities of the heterotrimeric subspecies, it was suggested that the inhibitory activity of the trimer was governed by one subunit with the highest activity, and not affected by the number of these subunits. The intermolecular electrostatic interactions between Glu23 and Lys28 of GbPLIα were also suggested to be important in stabilizing the trimeric structure. The importance of the electrostatic interaction was supported by the less stability of the homotrimeric structure of a mutant GbPLIα with a single amino acid substitution, GbPLIα(K28E).

Mapping the region of the alpha-type phospholipase A2 inhibitor responsible for its inhibitory activity.

alpha-Type phospholipase A(2) inhibitory protein (PLIalpha) from the serum of the venomous snake Gloydius brevicaudus, GbPLIalpha,isone of the protective endogenous proteins that neutralizes its own venom phospholipase A(2) (PLA(2)), and it is a homotrimer of subunits having a C-type lectin-like domain. The nonvenomous snake Elaphe quadrivirgata has a homologous serum protein, EqPLIalpha-LP, that does not show any inhibitory activity against various snake venom PLA(2)s (Okumura, K., Inoue, S., Ikeda, K., and Hayashi, K. (2003) IUBMB Life 55, 539-545). By constructing GbPLIalpha-Eq- PLIalpha-LP chimeric proteins, we have mapped the residues important in conferring GbPLIalpha inhibitory activity on region 13-36 in the primary structure of GbPLIalpha. Noninhibitory EqPLIalpha-LP showed comparable inhibitory activity only when this region was replaced with that of GbPLIalpha. Further, mutational analysis of the candidate residues revealed that the individual GbPLIalpha to EqPLIalpha-LP residue substitutions N26K, K28E, D29N, and Y144S each produced a mutant GbPLIalpha protein with reduced inhibitory activity, with the single N26K substitution having the most significant effect. Residues 13-36 were suspected to be located in the helical neck region of the GbPLIalpha trimer. Therefore, the region of GbPLIalpha responsible for PLA(2) inhibition was distinct from the carbohydrate-binding site of the homologous C-type lectin.